The long-range goal of this research is to understand the molecular basis of cell proliferation and how it is deranged in cancer cells. The focus of the grant is on the molecular and biochemical aspects of cell cycle control during exit from mitosis. The unfertilized eggs of vertebrates are arrested in metaphase by an activity known as cytostatic factor (CSF). CSF arrest can be elicited by expression of components of the MAPK pathway, including the MAPK substrate p9ORsk. p90Rsk phosphorylates and activates the spindle assembly checkpoint component Bub1. Bub1 activity has been linked to inhibition of the anaphase-promoting complex, which targets key proteins for degradation at the metaphase/anaphase transition. Experiments will evaluate whether Bub1 mediates CSF arrest by the MAPK pathway. This work provides a link between the MAPK/Rsk pathway and checkpoint control of the cell cycle at the metaphase/anaphase transition.